Extensive research has documented strong associations between alcohol and tobacco use. Various mechanisms have been invoked to explain a dual addiction to alcohol and nicotine, as well as the strong association between alcohol and tobacco intake across a range of consumption levels. Among them, behavioral models assert that associative learning occurs as a consequence of the frequent contemporaneous use of these two drugs. Using these models as a conceptual framework, preliminary work in our laboratory has demonstrated that alcohol cues and smoking cues elicit both strong cravings to drink alcohol and cravings to smoke (i.e., "cross-cue reactivity") in alcoholic smokers. Similar patterns, albeit to a lesser extent, were observed in alcoholic non- smokers and non-alcoholic smokers. The work proposed in this competitive continuation application extends this line of research by examining the separate and combined influence of alcohol/nicotine intake and salient substance cues on a broad range of subjective, physiological, and behavioral reactions. Using primarily within-subjects design features and established placebo control drug administration methods, Study 1 will investigate cravings and physiological reactivity to pictorial alcohol, smoking, and neutral cues in the presence of alcohol and/or nicotine. Study 2 will further examine the influence of alcohol and nicotine drug/cue manipulations on alcohol self- administration. Both studies will examine subjects across a broad range of alcohol and tobacco use patterns, and statistical models will evaluate the extent to which pharmacological and cue- based effects are influenced by individual differences in alcohol and tobacco intake. Overall, the proposed research will provide valuable basic data regarding the separate and combined influences of alcohol, nicotine, and relevant cues on multidimensional aspects of alcohol and smoking cue reactivity.